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Defective minor spliceosomes induce SMA-associated phenotypes through sensitive intron-containing neural genes in Drosophila.
Li, Liang; Ding, Zhan; Pang, Ting-Lin; Zhang, Bei; Li, Chen-Hui; Liang, An-Min; Wang, Yu-Ru; Zhou, Yu; Fan, Yu-Jie; Xu, Yong-Zhen.
Afiliação
  • Li L; Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences, Shanghai, 200032, China.
  • Ding Z; University of Chinese Academy of Sciences, Shanghai, 200032, China.
  • Pang TL; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Hubei, 430072, China.
  • Zhang B; Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences, Shanghai, 200032, China.
  • Li CH; University of Chinese Academy of Sciences, Shanghai, 200032, China.
  • Liang AM; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Hubei, 430072, China.
  • Wang YR; Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences, Shanghai, 200032, China.
  • Zhou Y; University of Chinese Academy of Sciences, Shanghai, 200032, China.
  • Fan YJ; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Hubei, 430072, China.
  • Xu YZ; Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences, Shanghai, 200032, China.
Nat Commun ; 11(1): 5608, 2020 11 05.
Article em En | MEDLINE | ID: mdl-33154379
The minor spliceosome is evolutionarily conserved in higher eukaryotes, but its biological significance remains poorly understood. Here, by precise CRISPR/Cas9-mediated disruption of the U12 and U6atac snRNAs, we report that a defective minor spliceosome is responsible for spinal muscular atrophy (SMA) associated phenotypes in Drosophila. Using a newly developed bioinformatic approach, we identified a large set of minor spliceosome-sensitive splicing events and demonstrate that three sensitive intron-containing neural genes, Pcyt2, Zmynd10, and Fas3, directly contribute to disease development as evidenced by the ability of their cDNAs to rescue the SMA-associated phenotypes in muscle development, neuromuscular junctions, and locomotion. Interestingly, many splice sites in sensitive introns are recognizable by both minor and major spliceosomes, suggesting a new mechanism of splicing regulation through competition between minor and major spliceosomes. These findings reveal a vital contribution of the minor spliceosome to SMA and to regulated splicing in animals.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Atrofia Muscular Espinal / Íntrons / Spliceossomos / Proteínas de Drosophila / Proteínas do Tecido Nervoso Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Atrofia Muscular Espinal / Íntrons / Spliceossomos / Proteínas de Drosophila / Proteínas do Tecido Nervoso Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China